BRAF, NRAS, KIT, TERT, GNAQ/GNA11 mutation profile analysis of head and neck mucosal melanomas: a study of 42 cases

Sarı, Serkan; Yılmaz, İsmail; Taşkin, Orhun Çığ; Narlı, Gizem; Şen, Fatma; Çomoğlu, Şenol; Firat, Pınar; Bılgıç, Bilge; Yılmazbayhan, Dilek; Büyükbabanı, Nesimi

doi:10.1016/j.pathol.2016.09.065

Cited by 41 publications

(41 citation statements)

References 52 publications

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“…Published studies have reported slightly lower overall mutation rates in head and neck mucosal melanoma (10–25%) (Chraybi et al , 2013; Zebary et al , 2013b; Lyu et al , 2016; Ozturk Sari et al , 2017) than that in the current study (40%); however, there was a considerably similar distribution of specific mutation rates in these studies: NRAS , 14%–60% BRAF , 0%–6% and KIT , 3%–12% (Cohen et al , 2004; Beadling et al , 2008; Carvajal et al , 2011; Turri-Zanoni et al , 2013; Zebary et al , 2013b). The Cancer Genome Atlas and other large-scale genomic analysis efforts in melanoma have identified hotspot NRAS mutations, thought to be important drivers of oncogenesis, in 25–30% of cutaneous melanomas (Akbani et al , 2015; Krauthammer et al , 2015).…”

Section: Discussioncontrasting

confidence: 78%

Mutation status among patients with sinonasal mucosal melanoma and its impact on survival

et al. 2017

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Background:Sinonasal mucosal melanoma (SNMM) comprises <1% of all melanomas and lacks well-characterised molecular markers. Our aim was to determine the frequencies of common mutations and examine their utility as molecular markers in a large series of primary SNMMs.Methods:SNMM patients seen at our institution from August 1991 through July 2016 were identified. Genomic DNA was extracted from 66 formalin-fixed paraffin-embedded tumours and screened for mutations by direct sequencing. We investigated the association of mutations with clinicopathological features and survival outcomes.Results:Overall, 41% (27 out of 66) of the SNMMs harboured mutations. BRAF and KIT mutations were identified in 8% (five patients) and 5% (three patients) of SNMMs, respectively, whereas NRAS mutations were detected in 30% (20 patients) of SNMMs. Mutation rates in these oncogenes were similar between SNMMs located in the paranasal sinuses and those in the nasal cavity (30% and 13%, respectively, P=0.09). In a multivariate analysis, patients with negative margins had significantly better overall survival (hazard ratio 5.43, 95% confidence interval 1.44–21.85, P=0.01) and disease-specific survival (hazard ratio 21.9, 95% confidence interval 3.71–180, P=0.0004). The mutation status of the tumours showed no association with survival outcomes.Conclusions:In SNNM, mutation status does not affect survival outcomes, but NRAS mutations are relatively frequent and could be targeted in this disease by MEK inhibitors.

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Section: Discussioncontrasting

confidence: 78%

Mutation status among patients with sinonasal mucosal melanoma and its impact on survival

et al. 2017

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“…The low MAPK mutation prevalence (16.1%) observed among POSNM samples is comparable with findings previously established by a Turkish group who also analysed the TERT and GNAQ/GNA11 oncogenes . Even though the overall mutation frequency among 41 POSNM individuals was 26%, the percentages of NRAS and BRAF mutations (4.8% each) were comparable to the 6.4% and 6.6% found in the present study.…”

Section: Discussionsupporting

confidence: 90%

“…Studies conducted in head and neck melanoma from different ethnic and geographic populations have shown NRAS mutation rates from 14% to 30% and comparable rates described in cutaneous tumours (18%‐20%) . Interestingly, the NRAS mutations observed at codon Q61 have been scarcely reported in other series . Thus, different patterns of NRAS mutations could be present in mucosal melanoma .…”

Section: Discussionmentioning

confidence: 95%

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CD117 immunoexpression in oral and sinonasal mucosal melanoma does not correlate with somatic driver mutations in the MAPK pathway

Maldonado‐Mendoza

Ramírez‐Amador

Anaya‐Saavedra

et al. 2019

J Oral Pathology Medicine

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Background Mutations on KIT and downstream genes of MAPK pathway that overstimulate cellular proliferation have been associated with primary oral and sinonasal melanomas (POSNM), but there is limited information that allows the use of personalized therapy. Thus, the aim of the present study was to determine a possible association between the C‐KIT immunohistochemical expression with the presence of somatic driver mutations in NRAS, BRAF, KIT, MITF and PTEN on POSNM. Methods A retrospective study included 62 tumour samples of an oncological reference centre in Mexico City (17‐year period). Immunohistochemistry stain of C‐KIT was carried out. Genomic DNA was obtained and used to assess hotspot mutations of KIT, NRAS, BRAF, MITF and PTEN through qPCR. Chi‐square, Fisher's exact and the Mann‐Whitney U tests were applied when necessary. The significance was set at P < 0.05. Results Sixty‐two cases were included, 74% were positive for C‐KIT immunoexpression, all exhibited moderate/strong intensity. Ten (16.1%) samples harboured at least one mutation, 6.4% and 6.6% for NRASQ61R and BRAFV600E, respectively, followed by KITK624E (3.2%). No KITL576P, MITF or PTEN mutations were identified. No significant correlation was observed between mutations and immunostaining (rs = −0.057, P = 0.765). Conclusions Regardless of the high immunoexpression of C‐KIT, there was no association with the MAPK mutations among POSNM samples. Thus, C‐KIT immunohistochemistry is not a reliable tool to detect POSNM candidates for biological therapy.

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“…While complete surgical excision offers the only prospect of cure, especially for mucosal melanoma of the nasal cavity, there is a high risk of surgical morbidity due to the challenging anatomical location, and most patients still develop incurable metastatic disease . The efficacy of immunotherapy (anti‐programmed death 1 [PD‐1] monoclonal antibody and/or anti‐cytotoxic T‐lymphocyte‐associated antigen 4 [CTLA‐4] monoclonal antibody) on mucosal melanoma is lower in comparison with cutaneous melanoma, as there are critical genetic differences that have not yet been fully explored, and mucosal melanoma rarely has BRAF mutations . Thus, the combination of radiotherapy (RT) and concomitant anti‐PD‐1 antibody therapy is often applied as the first‐line treatment for mucosal melanoma of the nasal cavity in our institute because preclinical data have shown that combinations of immune checkpoint inhibitors (ICI) and RT improved the response of these patients …”

Section: Introductionmentioning

confidence: 99%

Local and disease control for nasal melanoma treated with radiation and concomitant anti‐programmed death 1 antibody

Hanaoka

Tanemura

Takafuji

et al. 2020

The Journal of Dermatology

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Mucosal melanoma of the nasal cavity is a rare disease that has been consistently associated with poor outcome. While complete surgical excision offers the only prospect of a cure, it is associated with a high risk of surgical morbidity due to the challenging anatomical location, and most patients still develop incurable metastatic disease. The efficacy of immunotherapy on mucosal melanoma is lower in comparison with cutaneous melanoma, and mucosal melanoma rarely has BRAF mutations. Although preclinical data have shown that combination treatment with immune checkpoint inhibitors and radiotherapy (RT) improve the response, there have been few reports on the combination of RT and anti‐programmed death 1 therapy for mucosal melanoma of the nasal cavity. We retrospectively investigated 10 cases of mucosal melanoma of the nasal cavity in which combined treatment was applied. The local control (LC) rate of the primary lesion and regional lymph nodes was favorably 100%. On the other hand, the median progression‐free survival (PFS) time was 29.6 weeks (range, 2–82). The 6‐month PFS rate was 60%. Although severe mucositis occurred in one patient, the incidence of treatment‐related adverse events was not significantly increased. RT with anti‐programmed death 1 antibody therapy for mucosal melanoma of the nasal cavity was tolerable and had the potential to improve LC and PFS.

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BRAF, NRAS, KIT, TERT, GNAQ/GNA11 mutation profile analysis of head and neck mucosal melanomas: a study of 42 cases

Cited by 41 publications

References 52 publications

Mutation status among patients with sinonasal mucosal melanoma and its impact on survival

Mutation status among patients with sinonasal mucosal melanoma and its impact on survival

CD117 immunoexpression in oral and sinonasal mucosal melanoma does not correlate with somatic driver mutations in the MAPK pathway

Local and disease control for nasal melanoma treated with radiation and concomitant anti‐programmed death 1 antibody

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